Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• , with the protecting groups removed except benzoyl. PTSA-catalyzed acetonization of 10 using 2.0 equiv DMP gave a mixture of two acetonides 19 and 13, which are separable by silica gel chromatography (Scheme 5a). In another trial (Scheme 5b), acylation of the two hydroxy groups in 9 yielded 20 in a

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• these conditions the acetate function was also hydrolyzed the carboxy group was formed by oxidation of the hydroxymethyl residue. To complete the synthesis N- and O-benzylic protecting groups were removed during the Birch reaction. A polyoxamic structural framework was found in polyoxins, natural

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• protected with the 2-cyanoethyl group. These protecting groups and the linker have to be cleaved under strongly basic and nucleophilic conditions. As a result, many sensitive groups including acetal, hemiacetal, vinyl ethers, enol ethers, aldehydes, esters, activated esters, thioesters, aziridines, epoxides

• especially for the synthesis of ODNs approaching 20-mer or longer, may not be easy to achieve. To develop a universal technology for the synthesis of ODNs that contain a wide variety of sensitive functionalities, we recently reported the use of 1,3-dithian-2-ylmethoxycabonyl (Dmoc) as protecting groups and

• that acceptable yields could be achieved under the highly reactive conditions involving two equivalents LDA and one equivalent 5. The silyl protecting groups were then removed with TBAF giving compound 11 in 99% yield. Tritylation of 11 with DMTrCl gave 12, which was phosphitylated with reagents 13 and

A three-component, Zn(OTf)₂-mediated entry into trisubstituted 2-aminoimidazoles

• Alexei Lukin,
• Anna Bakholdina,
• Anna Kryukova,
• Alexander Sapegin and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2019, 15, 1061–1064, doi:10.3762/bjoc.15.103

• isocyanates. However, its scope is limited to aliphatic amines as the reaction failed to work for anilines (even electron-rich ones, such as p-anisidine). The tolerance of acid-labile protecting groups such as Boc is particularly useful as it offers an opportunity for further side-chain modifications. From

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• to prevent the binding to primary sites. Conclusion A series of glucose and N-acetyl glucosamine-based thioglycolipids were synthesized for the first time by using thiol–ene coupling in the absence of protecting groups and in good yields. Monosaccharides where selected on the basis of similar

Tuning the stability of alkoxyisopropyl protection groups

• Zehong Liang,
• Henna Koivikko,
• Mikko Oivanen and
• Petri Heinonen

Beilstein J. Org. Chem. 2019, 15, 746–751, doi:10.3762/bjoc.15.70

• Zehong Liang Henna Koivikko Mikko Oivanen Petri Heinonen Department of Chemistry, University of Helsinki, P.O.Box 55 (A.I.Virtasen aukio 1), FIN-00014 Helsinki, Finland 10.3762/bjoc.15.70 Abstract Five different 2-alkoxypropan-2-yl groups are introduced as acid-labile protecting groups for the 5

• ’- and 3’-hydroxy groups of a 2’-deoxynucleoside. All studied protecting groups were readily introduced with good to excellent yields using the appropriate enol ether as a reagent and 0.5 to 1 mol % p-toluenesulfonic acid as a catalyst. The protected compounds could be purified by silica gel column

• chromatography without degradation. The compatibility of these protecting groups in parallel use with benzoyl and silyl groups was verified. The stabilities of the different alkoxy acetal protecting groups were compared by following the kinetics of their hydrolysis at 25.0 °C in buffered solutions through an

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• -substituted OPA synthesis represents a major limiting factor to their potential applications. Herein, we set forth a new protection-deprotection strategy which leads to 4-MeO-OPA and 4-HO-OPA as reliable structures for organic and analytical chemistries. A variety of protecting groups of key 4,5

• protecting group described in the literature for 4,5-dihydroisobenzofuran-5-ol (3) is acetyl [19]. Thus, beside this former, several protecting groups such as: methyl (Me), benzyl (Bn), tert-butyldimethylsilyl (TBDMS) and trimethylsilyl (TMS) were tested (Scheme 2). As summarized in Table 1, major disparity

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• installation of designed disulfonyl capping moieties to the CD core and their subsequent substitution by the desired functional groups or (ii) the indirect difunctionalization based on the regioselective removal of protecting groups from a previously perfunctionalized CD derivative. The first approach was

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• dendrimer. Therefore, we settled on first coupling Nα-Fmoc-Nε-(4-methyltrityl)-L-lysine (17) to the dendrimeric amine 18 by standard HATU amide coupling conditions (Scheme 3). The protecting groups were chosen specifically for selective deprotection and compatibility with the TAMRA fluorophore, which is

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• , the yield was lower (Scheme 2). In order to bring about the cleavage of the benzyl protecting groups in the ketones 8a and 8b by hydrogenolysis [17][18], various metal catalysts were tested. It turned out that palladium on charcoal was the only catalytic system that provided satisfying results. Ethyl

• , 69.56; H, 6.73. General procedure for the synthesis of phenols 9–11 by hydrogenolytic cleavage of benzyl ether protecting groups: An autoclave was equipped with a stirring bar and charged with O-protected dihydrostilbenes 8a,b (0.8 mmol), palladium on charcoal (50 mg) and ethyl acetate (12 mL). The

• -catalyzed addition of ketones 6 to styrenes 7. Yields: 8a: 65%; 8b: 68%; 8c: 73%; 8d: 40%. Cleavage of benzyl protecting groups in ketones 8a and 8b. Synthesis of scorzodihydrostilbene aglycon 9. Synthesis of glycoside 12 and deprotected epi-scorzodihydrostilbene D (13). Yields of isolated products: 12: 14

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• components can significantly diversify the synthetic output of MMCRs. However, a limiting factor in the design of MMCRs with such components is the risk of generating undesired cross-adducts. This problem can be avoided by introduction of protecting groups or through the sequential generation of repeating

• course of a given MCR can trigger a new one, then allowing for selectivity in another sequential approach. Finally, the use of protecting groups in reactants undergoing MCRs leads to multistep transformations which, after suitable deprotections, selectively afford the final adducts. Active research is

• pursued in the field, aiming at the generalization of the aforementioned concepts and their extension to diverse synthetic outcomes. Selectivity levels found in multiple multicomponent reactions. I) Innate selectivity; II) sequential selectivity; III) use of biased substrates; IV) use of protecting groups

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• in the β-anomer form ( −58.7°) in 62% yield, while the benzoylated analogue 4b ( −44.0°) was obtained in lower yields of 40% (Scheme 1). Acetyl and benzoyl protecting groups were then removed from 4a and 4b in anhydrous methanol saturated with dry ammonia at 0 °C, to afford NR+Cl− ( −28.6°) in good

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• ). Dihydroxylation of the C=C bond gave a 10:1 mixture with (2S,3S,4R)-121 as a major product which was transformed into the isopropylidene derivative (2S,3S,4R)-122 to facilitate purification. Hydrogenolysis allowed to remove the N- and O-protecting groups and was followed by the spontaneous cyclization to a

• compound underwent another intramolecular cyclization in the 5-exo mode to form the oxazolidinone 118. To complete the synthesis of (2S,3S,4S)-4 the secondary hydroxy group was protected as a pivalate, the hydroxymethyl fragment was oxidized after hydrolysis of the silyl ether and finally all protecting

• groups were removed by concentrated acid. A very efficient synthesis of (2S,3S,4S)-4 starts from another serine-derived chiron, namely O-benzyl-N-Boc-D-serine [111], which was readily transformed to the Z-olefin 120 containing a benzophenone imine residue as a nitrogen protecting group (Scheme 29

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• group was the key for the high efficiency of this coupling. Similarly, condensation between peracylated GlcA donor 3 and 4 gave disaccharide 5 in excellent 97% yield (Scheme 2). The cyclic silylene group was then replaced by two acetyl groups because it is well-known that cyclic protecting groups at

• % of TMSOTf with respect to the donor, 0 ºC, CH2Cl2 as solvent). As mentioned before, it has been reported that cyclic protecting groups like 4,6-O-benzylidene acetals in GalNAc trichloroacetimidates lead to the formation of α/β mixtures in glycosylations involving GlcA acceptors [43][47]. However

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• -protecting groups, such as a benzyl group, at either the donor, the acceptor or at both. With the 6-O-Bn donor 16 a slightly diminished, but still respectable, 49% yield of the desired product 19 was obtained (Scheme 3). However, when using the 6-O-TBDPS donor 15 (1.2 equiv) a 60% isolated yield of the

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• in high chemical yield and purity by strategically introducing differentially protected dibasic amino acids such as lysine whose α- and ε-amino groups are protected as base labile Fmoc and trifluoroacetyl (Tfa) protecting groups, respectively. The whole concept is successfully illustrated using

• commonly available and less expensive cysteine-labelled 2-chlorotrityl resin (Figure 1b). The methodology is general and can be significantly useful for acid-sensitive resins that contain acid-labile orthogonal amino acids with 4-methoxytrityl (Mmt) and 4-methyltrityl (Mtt) protecting groups. Results and

• (Pg) to give tetrapeptides 8a or 8b. The tetrapeptides 8a or 8b were tethered sequentially to 8-aminocaprylic acid, two phenyalanine residues, another 8-aminocaprylic acid and finally to DUPA precursor 4, to provide polypeptide chains 9a or 9b (Scheme 2). The ε-amino protecting groups present in the

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• functionalised phenothiazine demonstrated an equipotent MIC value in direct comparison to the parent phenothiazine from which it was derived. The final conjugate was synthesised by amide bond formation between the two components and global deprotection of the PMB protecting groups to unmask the catechol iron

• azotochelin. Catechol-based siderophores can act as xenosiderophores and be recognised for uptake by Gram-negative bacteria and mycobacteria [14][15]. Most commonly benzyl protecting groups are used in the synthesis of catechol siderophores and cleaved in the final step by palladium catalysed hydrogenation

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• , avoiding the use of protecting groups, and affording the desired heterocycles in good to excellent overall yields. A suitable balance between reactivity and selectivity was achieved in the SNAr reaction which, to our knowledge, is the first report on a successful uncatalyzed N-monoarylation of the

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• hand, we finally accomplished the N-acylation reaction using n-BuLi in THF at −60 °C [15] in 60% yield. Removal of both protecting groups by catalytic hydrogenation, gave the desired compound 1 in 72% yield (Scheme 3). Compound 1 was subjected to a preliminary study to evaluate the antimicrobial

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• Organische Chemie, Universität Münster, Corrensstrasse 40, 48149 Münster, Germany 10.3762/bjoc.14.217 Abstract Copper(I)-promoted "click" cyclization in the presence of TBTA afforded nucleoside macrocycles in very high yields (≈70%) without using protecting groups. To this end, dU and dC derivatives

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• with different protecting groups, resulting in cumbersome steps and high costs. To reduce the synthetic steps and simplify the operations, we developed a new semi-synthesis of spinetoram J based on a self-protection strategy (Scheme 2). In this study, 3-O-ethyl-2,4-di-O-methylrhamnose was used not only

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• was converted to 6a as previously described in [23]. Next, the isopropylidene group at positions 4 and 5 were removed under acidic conditions and the resulting intermediate 7a was converted to 7b with identical protecting groups at positions 3, 4 and 5 [24][25][26][27][28]. In order to obtain D

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• protected naturally occurring amines such as GABA and phenylethylamine as well as diamines with orthogonal protecting groups, cf. product 2c. The combination of this protocol with the diastereoselective reductive amination reported by Hughes and Devine [41], provides access to very high value chiral α

An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

• . Deprotection was performed by oxidation followed by treating with a weak base. The yields were good to excellent. The new amino protecting group offers a different dimension of orthogonality in reference to the commonly used amino protecting groups in terms of deprotection conditions. It is expected to allow a

• collection of transformations to be carried out on the protected substrates that are unattainable using any known protecting groups. Keywords: amine; carbamate; dM-Dmoc; oxidation; protecting group; Introduction In multistep organic synthesis, amino groups usually have to be protected [1]. Protecting

• groups for the purpose mainly include those deprotectable by acid (e.g., tert-butyloxycarbonyl (Boc) group) [2][3][4], base (e.g., 9-fluorenylmethyloxycarbonyl (Fmoc) group and trifluoroacetyl group) [5][6][7], catalytic hydrogenation (e.g., benzyl group) [8], photoirradiation (e.g., 2-nitrophenylethyl

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• reaction with phenol to stereoselectively achieve the respective β-mannoside 82 in good yield (Scheme 14) [60]. This stereo-differentiating effect of isopropylidene protecting groups was also observed in other cases with D-mannopyranose [46][61]. It might be used as a key to a reliable approach to

• otherwise difficult to synthesize β-mannosides using the Mitsunobu procedure. This approach to 1,2-cis-mannosides is equally effective when cyclohexylidene protecting groups are used [28][47][62]. Mitsunobu glycosylation was also a successful method in total synthesis. In the course of a 17-step synthesis

• of hygromycin A, Donohoe et al. used a Mitsunobu glycosylation of 84 with the arabinose derivative 83. This reaction could be tuned to deliver the required β-arabinofuranoside building block 85 with high stereoselectivity and under the assistance of triisopropylsilyl (TIPS) protecting groups (Scheme